P536: VALUE OF MEASURABLE RESIDUAL DISEASE BY MULTIPARAMETRIC FLOW CYTOMETRY IN NON-PROMYELOCYTIC ACUTE MYELOID LEUKEMIA. REAL WORLD EVIDENCE
Authors: A. D. Gimenez Conca, J. Gonzalez, M. M. Rivas, A. Navickas, I. Fernandez, I. Rey, H. Dick, S. Cranco, M. Moirano, L. Ferrari, M. Clavijo, A. Suero, R. Ramirez, A. L. Basquiera, N. Carnelutto, M. L. Rapan, A. Jorge Alberto, C. Belli
Journal: HemaSphere (2022)

Background: Measurable residual disease (MRD) allows recognition of a group of patients with acute myeloid leukemia (AML) with a higher risk of relapse. There are, however, remaining open questions, since clinical studies applied variable techniques, cutoff values and time points. Multiparameter flow cytometry (MFC) is the most accessible method in Argentina, since real time PCR assessment is not available for the majority of the institutions. We designed, therefore, this real-life study using decentralized assessment of MRD by MFC to solve the role of positive MRD at different times during treatment with standard chemotherapy. Aims: Our aim was to assess the impact of positive MRD at the end of induction and after first consolidation (C1) as a prognostic factor for relapse-free survival (RFS) and overall survival (OS) in patients with non-promyelocytic AML. Methods: The registry of the Argentinian Group of Acute Leukemia (GALA) from the Argentine Society of Hematology (SAH) includes data from 20 centers. We retrospectively selected an analytical cohort with all patients with AML, treated with an intensive regimen and in complete remission (CR) after induction, from January 2010 to March 2021. The OS and RFS were estimated with Kaplan-Meier method and its comparison was evaluated by log-rank, censoring patients at the time of bone marrow transplantation (BMT). The cut-off point for MRD analysis was 0.1% evaluated at the end of induction and after C1. A subanalysis of patients with unknown and intermediate cytogenetic risk (CRM modified according to available molecular data of FLT3, NPM1 and CEBPA) was performed. Results: Of the 1,160 patients enrolled in the registry, 493 met the inclusion criteria and 20 were excluded due to lack of MRD data at the end of induction. Among the 473 patients analyzed: 238 were women, the median age was 49.5 years [IQR 36.6-59.7]), 184 (38.9%) were intermediate risk and 51 (10.8%) with not evaluable cytogenetic and molecular data. With a median follow-up of 18.9 months, 158 (33.4%) relapsed and 130 (27.5%) died. The median (Me) OS for patients with post induction negative MRD (MRDneg) was 61.2 (CI95% not evaluable) versus 25.9 months (CI95% 2.5-49.2) with positive MRDpos, p =0.03. The RFS were 20.4 (CI95 8-32.8) and 12.4 (CI95% 6.5-18.3), p=0.06, for MRDneg and MRDpos respectively. Regarding the evaluation of MRD post C1, the Me OS was not reached for patients with MRDneg, while it was 22.1 months (CI95% 9.3-34.8) among patients with MRDpos, p=0.03. Their respective RFS were 30.3 (CI95% not evaluable) and 14.4 months (CI95% 0-30.7), p=0.03, respectively. In the subanalysis carried out in the group with intermediate or unknown cytogenetic risk post C1, the Me OS was not reached in MRDneg versus 17.5 months (CI95% 9.3-25.7) in MRDpos, p=0.007. In addition, a median RFS of 20.4 months (CI95% 0.7-40.1) vs 7.4 (CI95% 3.9-10.9), p=0.003, among those with MRDneg and MRDpos, respectively. Summary/Conclusion: The assessment of MRD by MFC showed predictive power at the different moments of follow-up evaluated. It was more evident after consolidation, with statistically significant impact in OS and RFS. The post-consolidation MRD subanalysis in the group with IR or non-evaluable cytogenetics showed promising results. This real-practice data is consistent with those published recently. Post-C1 MRD could be a useful tool in clinical practice deciding the best post-induction strategy in intermediate-risk patients. A further detailed study is required to confirm our preliminary results.